The recent clinical activity in lung transplantation coupled with our limited understanding of metabolism in toxic lung injury have prompted a renewed interest in assessing pulmonary metabolism. However, since the concentration and metabolic rate of pneumocytes is low, it was not clear whether NMR methods could be used to study intermediary metabolism in lung tissue. Rats received a 45 minute infusion of 3 ml of 1.67 M [3-13C] lactate and 0.83 M [1,2-13C] acetate in water via the femoral vein. At the conclusion of the infusion period, lung and heart tissue were excised, separated, freeze-clamped, and extracted. Relative substrate utilization was then determined using isotopomer analysis of the resulting 13C NMR spectra. Both heart and lung were found to oxidize lactate and acetate, although a substantial amount of unlabeled substrates were also utilized. There were no significant differences between lung and heart in the relative contributions of lactate, acetate, and unlabeled sources to acetyl-CoA metabolized within the citric acid cycle. However, multiplet peaks arising from second or later turns of the cycle were more prominent in cardiac tissue extracts. These spectra indicate that at least some cells are oxidizing both lactate and acetate. The differences in spectra from the heart and lungs of the same animal are due either to much lower oxygen consumption in lung compared to heart tissue, or differences in metabolic pool sizes. Although these possibilities can not be distinguished with current data, the former is more likely. (Collaborative 8) REPORT PERIOD: (09/01/97-08/31/98)